Dexedrine

WARNINGS

Serious Cardiovascular Events

Sudden Death in Patients With Pre-existing Structural
Cardiac Abnormalities or Other Serious Heart Problems

Children and Adolescents

Sudden death has been reported in association with CNS
stimulant treatment at usual doses in children and adolescents with structural
cardiac abnormalities or other serious heart problems. Although some serious
heart problems alone carry an increased risk of sudden death, stimulant
products generally should not be used in children or adolescents with known
serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm
abnormalities, or other serious cardiac problems that may place them at
increased vulnerability to the sympathomimetic effects of a stimulant drug.

Adults

Sudden deaths, stroke, and myocardial infarction have
been reported in adults taking stimulant drugs at usual doses for ADHD.
Although the role of stimulants in these adult cases is also unknown, adults
have a greater likelihood than children of having serious structural cardiac
abnormalities, cardiomyopathy, serious heart rhythm abnormalities, coronary
artery disease, or other serious cardiac problems. Adults with such
abnormalities should also generally not be treated with stimulant drugs (see CONTRAINDICATIONS).

Hypertension And Other Cardiovascular Conditions

Stimulant medications cause a modest increase in average
blood pressure (about 2-4 mmHg) and average heart rate (about 3-6 bpm), and
individuals may have larger increases. While the mean changes alone would not
be expected to have short-term consequences, all patients should be monitored
for larger changes in heart rate and blood pressure. Caution is indicated in
treating patients whose underlying medical conditions might be compromised by
increases in blood pressure or heart rate, e.g., those with pre-existing hypertension,
heart failure, recent myocardial infarction, or ventriculararrhythmia (see CONTRAINDICATIONS).

Assessing Cardiovascular Status In Patients Being Treated
With Stimulant Medications

Children, adolescents, or adults who are being considered
for treatment with stimulant medications should have a careful history
(including assessment for a family history of sudden death or ventricular
arrhythmia) and physical exam to assess for the presence of cardiac disease,
and should receive further cardiac evaluation if findings suggest such disease
(e.g., electrocardiogram and echocardiogram). Patients who develop symptoms
such as exertional chest pain, unexplained syncope, or other symptoms suggestive
of cardiac disease during stimulant treatment should undergo a prompt cardiac
evaluation.

Psychiatric Adverse Events

Pre-Existing Psychosis

Administration of stimulants may exacerbate symptoms of
behavior disturbance and thought disorder in patients with a pre-existing
psychotic disorder.

Bipolar Illness

Particular care should be taken in using stimulants to
treat ADHD in patients with comorbid bipolar disorder because of concern for
possible induction of a mixed/manic episode in such patients. Prior to
initiating treatment with a stimulant, patients with comorbid depressive
symptoms should be adequately screened to determine if they are at risk for
bipolar disorder; such screening should include a detailed psychiatric history,
including a family history of suicide, bipolar disorder, and depression.

Emergence Of New Psychotic Or Manic Symptoms

Treatment emergent psychotic or manic symptoms, e.g.,
hallucinations, delusional thinking, or mania in children and adolescents
without a prior history of psychotic illness or mania can be caused by
stimulants at usual doses. If such symptoms occur, consideration should be
given to a possible causal role of the stimulant, and discontinuation of
treatment may be appropriate. In a pooled analysis of multiple short-term,
placebo-controlled studies, such symptoms occurred in about 0.1% (4 patients
with events out of 3,482 exposed to methylphenidate or amphetamine for several
weeks at usual doses) of stimulant-treated patients compared to 0 in
placebo-treated patients.

Aggression

Aggressive behavior or hostility is often observed in
children and adolescents with ADHD, and has been reported in clinical trials
and the postmarketing experience of some medications indicated for the
treatment of ADHD. Although there is no systematic evidence that stimulants
cause aggressive behavior or hostility, patients beginning treatment for ADHD
should be monitored for the appearance of, or worsening of, aggressive behavior
or hostility.

Long-Term Suppression Of Growth

Careful follow-up of weight and height in children ages 7
to 10 years who were randomized to either methylphenidate or non- medication
treatment groups over 14 months, as well as in naturalistic subgroups of newly
methylphenidate-treated and non-medication treated children older than 36
months (to the ages of 10 to 13 years), suggests that consistently medicated children
(i.e., treatment for 7 days per week throughout the year) have a temporary
slowing in growth rate (on average, a total of about 2 cm less growth in height
and 2.7 kg less growth in weight over 3 years), without evidence of growth
rebound during this period of development. Published data are inadequate to
determine whether chronic use of amphetamines may cause a similar suppression
of growth, however, it is anticipated that they likely have this effect as
well. Therefore, growth should be monitored during treatment with stimulants,
and patients who are not growing or gaining height or weight as expected may
need to have their treatment interrupted.

Seizures

There is some clinical evidence that stimulants may lower
the convulsive threshold in patients with prior history of seizures, in
patients with prior EEG abnormalities in absence of seizures, and, very rarely,
in patients without a history of seizures and no prior EEG evidence of
seizures. In the presence of seizures, the drug should be discontinued.

Peripheral Vasculopathy, Including Raynaud's phenomenon

Stimulants, including DEXEDRINE, used to treat ADHD are
associated with peripheral vasculopathy, including Raynaud's phenomenon. Signs
and symptoms are usually intermittent and mild; however, very rare sequelae
include digital ulceration and/or soft tissue breakdown. Effects of peripheral
vasculopathy, including Raynaud's phenomenon, were observed in post-marketing
reports at different times and at therapeutic doses in all age groups
throughout the course of treatment. Signs and symptoms generally improve after
reduction in dose or discontinuation of drug. Careful observation for digital
changes is necessary during treatment with ADHD stimulants. Further clinical
evaluation (e.g., rheumatology referral) may be appropriate for certain
patients.

Visual Disturbance

Difficulties with accommodation and blurring of vision
have been reported with stimulant treatment.

PRECAUTIONS

General

The least amount feasible should be prescribed or
dispensed at 1 time in order to minimize the possibility of overdosage.

Information for Patients

Amphetamines may impair the ability of the patient to
engage in potentially hazardous activities such as operating machinery or
vehicles; the patient should therefore be cautioned accordingly.

Prescribers or other health professionals should inform
patients, their families, and their caregivers about the benefits and risks associated
with treatment with dextroamphetamine and should counsel them in its
appropriate use. A patient Medication Guide is available for DEXEDRINE. The
prescriber or health professional should instruct patients, their families, and
their caregivers to read the Medication Guide and should assist them in
understanding its contents. Patients should be given the opportunity to discuss
the contents of the Medication Guide and to obtain answers to any questions
they may have. The complete text of the Medication Guide is reprinted at the
end of this document.

Instruct patients beginning treatment with DEXEDRINE
about the risk of peripheral vasculopathy, including Raynaud's phenomenon, and
associated signs and symptoms: fingers or toes may feel numb, cool, painful,
and/or may change color from pale, to blue, to red.

Instruct patients to report to their physician any new
numbness, pain, skin color change, or sensitivity to temperature in fingers or
toes.

Instruct patients to call their physician immediately
with any signs of unexplained wounds appearing on fingers or toes while taking
DEXEDRINE.

Further clinical evaluation (e.g., rheumatology referral)
may be appropriate for certain patients.

Carcinogenesis/Mutagenesis

Mutagenicity studies and long-term studies in animals to
determine the carcinogenic potential of DEXEDRINE have not been performed.

Pregnancy

Teratogenic Effects

Pregnancy Category C

DEXEDRINE has been shown to have embryotoxic and
teratogenic effects when administered to A/Jax mice and C57BL mice in doses
approximately 41 times the maximum human dose. Embryotoxic effects were not
seen in New Zealand white rabbits given the drug in doses 7 times the human
dose nor in rats given 12.5 times the maximum human dose. While there are no
adequate and well-controlled studies in pregnant women, there has been 1 report
of severe congenital bony deformity, tracheoesophageal fistula, and anal
atresia (VATER association) in a baby born to a woman who took
dextroamphetamine sulfate with lovastatin during the first trimester of
pregnancy. DEXEDRINE should be used during pregnancy only if the potential
benefit justifies the potential risk to the fetus.

Nonteratogenic Effects

Infants born to mothers dependent on amphetamines have an
increased risk of premature delivery and low birth weight. Also, these infants
may experience symptoms of withdrawal as demonstrated by dysphoria, including
agitation, and significant lassitude.

Nursing Mothers

Amphetamines are excreted in human milk. Mothers taking
amphetamines should be advised to refrain from nursing.

Pediatric Use

Long-term effects of amphetamines in pediatric patients
have not been well established. DEXEDRINE is not recommended for use in pediatric
patients younger than 6 years of age with Attention Deficit Disorder with
Hyperactivity described under INDICATIONS AND USAGE. Clinical experience
suggests that in psychotic children, administration of amphetamines may
exacerbate symptoms of behavior disturbance and thought disorder. Amphetamines
have been reported to exacerbate motor and phonic tics and Tourette's syndrome.
Therefore, clinical evaluation for tics and Tourette's syndrome in children and
their families should precede use of stimulant medications. Data are inadequate
to determine whether chronic administration of amphetamines may be associated
with growth inhibition; therefore, growth should be monitored during treatment.
Drug treatment is not indicated in all cases of Attention Deficit Disorder with
Hyperactivity and should be considered only in light of the complete history
and evaluation of the child. The decision to prescribe amphetamines should
depend on the physician's assessment of the chronicity and severity of the
child's symptoms and their appropriateness for his or her age. Prescription
should not depend solely on the presence of one or more of the behavioral
characteristics. When these symptoms are associated with acute stress
reactions, treatment with amphetamines is usually not indicated.

Last reviewed on RxList: 12/19/2013
This monograph has been modified to include the generic and brand name in many instances.